µ-Opioid Activity in Chronic TMD Pain Is Associated with COMT Polymorphism.

Clinicians have the dilemma of prescribing opioid or nonopioid analgesics to chronic pain patients; however, the impact of pain on our endogenous µ-opioid system and how our genetic profile (specifically catechol-O-methyltransferase [COMT] polymorphisms) impacts its activation are currently unknown. Twelve chronic temporomandibular disorder (TMD) patients and 12 healthy controls (HCs) were scanned using positron emission tomography (PET) with [11C]carfentanil, a selective radioligand for µ-opioid receptors (µORs). The first 45 min of each PET measured the µOR nondisplaceable binding potential (BPND) at resting state, and the last 45 min consisted of a 20-min masseteric pain challenge with an injection of 5% hypertonic saline. Participants were also genotyped for different COMT alleles. There were no group differences in µOR BPND at resting state (early phase). However, during the masseteric pain challenge (late phase), TMD patients exhibited significant reductions in µOR BPND (decreased [11C]carfentanil binding) in the contralateral parahippocampus (P = 0.002) compared to HCs. The µOR BPND was also significantly lower in TMD patients with longer pain chronicity (P < 0.001). When considering COMT genotype and chronic pain suffering, TMD patients with the COMT158Met substitution had higher pain sensitivity and longer pain chronicity with a 5-y threshold for µOR BPND changes to occur in the parahippocampus. Together, the TMD diagnosis, COMT158Met substitution, and pain chronicity explained 52% of µOR BPND variance in the parahippocampus (cumulative R2 = 52%, P < 0.003, and HC vs. TMD Cohen's effect size d = 1.33 SD). There is strong evidence of dysregulation of our main analgesic and limbic systems in chronic TMD pain. The data also support precision medicine by helping identify TMD patients who may be more susceptible to chronic pain sensitivity and opioid dysfunction based on their genetic profile.

In-vitro fertilisation treatment: factors affecting its results and outcome.

The objective of this study was to determine factors affecting results and outcome of in-vitro fertilisation (IVF). In this retrospective study, a total of 891 infertile women underwent IVF/ICSI cycles at the King Hussein Medical Center (KHMC) between January 2001 and December 2002. Conventional IVF treatment was performed in 64.6% of women and intracytoplasmic sperm injection (ICSI) in 35.4%, using a standardised long luteal protocol. Pregnancy rate was analysed according to age, type of infertility, cause of infertility, duration of infertility, number of eggs collected and follicle stimulating hormone (FSH) levels. A total of 126 cycles (14.1%) were cancelled. Among 765 cycles continued, fertilisation rate was 73.9%, implantation rate was 15.1% and pregnancy rate was 29.8%. Pregnant women had a multiple pregnancy rate of 28.9%, abortion rate of 13.6% and ectopic pregnancy rate of 1.3%. Duration and type of infertility had no significant effect on the pregnancy rate. Factors which appear to affect significantly the outcome of treatment include the woman's age, cause of infertility, basal concentrations of FSH, adequate ovarian responsiveness and the number of eggs collected. In some cases with poor outcome, the understanding of these factors may predict the results and lead to the development of new strategies to improve the outcome of IVF treatment.